[Therapeutic options for oligoprogressive non-small cell lung cancer]. / Prise en charge thérapeutique des cancers bronchiques non à petites cellules oligoprogressifs.

Lung cancer is the leading cause of cancer-related mortality and more than half of the cases are diagnosed at a metastatic stage. Major progress in terms of systemic treatments has been achieved in recent decades. Access to new anti-PD-(L) 1 immunotherapies and targeted therapies for non-small cell lung cancer (NSCLC) with oncogenic addiction such as EGFR mutation or ALK rearrangement have led to improved outcomes. Patients with limited progression of their disease during systemic treatment may be a particular subgroup. This oligoprogressive state is characterized by a limited number of sites in progression, implying that the other sites remain controlled and therefore sensitive to systemic treatments. The advent of non-invasive techniques such as stereotactic radiotherapy, radiofrequency, and mini-invasive surgery has led to a precise re-evaluation of local ablative treatments in this situation. Local treatment of the oligoprogressive lesion(s) may allow modification of the natural history of the disease, maintenance of effective systemic targeted treatment and, ultimately, to improved survival. Data validating an aggressive local therapeutic approach in oligoprogressive NSCLC patients are currently limited and essentially retrospective. Several international trials are underway that could confirm the clinical benefit of radical local treatment in oligoprogressive advanced NSCLC patients.

The use of antibiotics in cattle in North-East Benin: pharmaceutical inventory and risk practices of cattle breeders.

This study's aim is to inventory antibiotics used in cattle in North-East Benin and assess risk practices that could be the cause of both food chain contamination by antibiotic residues and selection of antibiotic-resistant bacteria in animals and humans. A survey was conducted among 98 cattle breeders in the districts of Banikoara, Kandi, Bembereke, and Kalale in North Benin. Semi-structured interviews were conducted, covering breeder status, breeding system, and antibiotic use. Multiple correspondence analysis and hierarchical classification analysis were conducted to establish a breeder typology. Breeders mainly belonged to the Fulani ethnic group (71.4 ± 8.9%) and almost all of them received "no formal education" (96.9 ± 3.4%). Cattle herds were mainly composed of a single breed, the Borgou (76.4 ± 8.1%) or the Fulani Zebu (16.0 ± 7.0%). Some herds were mixed. Antibiotics groups used in cattle breeding were tetracyclines, beta-lactams, sulfonamides, aminoglycosides, and macrolides, used by respectively 100%, 69.4 ± 9.1%, 56.1 ± 9.8%, 44.9 ± 9.8%, and 34.7 ± 9.4% of breeders. These drugs were purchased in local markets (59.0 ± 15.4%) and veterinary pharmacy (41.0 ± 15.4%). They were mainly used against respiratory diseases, lameness, mastitis, omphalitis and neonatal enteritis, and skin diseases. Only 49.0 ± 9.9% of breeders seek veterinary services to treat animals and 92.9 ± 5.1% of them did not respect antibiotic withdrawal times. These practices suggest that both contamination of bovine meat with antibiotic residues and selection of resistant bacteria are to be expected, resulting in adverse health effects on consumers.

[Prognostic value of the metabolically active tumour volume]. / Valeur pronostique du volume tumoral métabolique sur la TEP au ((18)F)-fluorodésoxyglucose préthérapeutique pour le cancer de l'œsophage localisé.

PURPOSE: The purpose of this study was to assess the prognostic value of different parameters on pretreatment fluorodeoxyglucose [((18)F)-FDG] positron emission tomography-computed tomography (PET-CT) in patients with localized oesophageal cancer. PATIENTS AND METHOD: We retrospectively reviewed 83 cases of localised oesophageal cancer treated in our institution. Patients were treated with curative intent and have received chemoradiotherapy alone or followed by surgery. Different prognostic parameters were correlated to survival: cancer-related factors, patient-related factors and parameters derived from PET-CT (maximum standardized uptake value [SUV max], metabolically active tumor volume either measured with an automatic segmentation software ["fuzzy locally adaptive bayesian": MATVFLAB] or with an adaptive threshold method [MATVseuil] and total lesion glycolysis [TLGFLAB and TLGseuil]). RESULTS: The median follow-up was 21.8 months (range: 0.16-104). The median overall survival was 22 months (95% confidence interval [95%CI]: 15.2-28.9). There were 67 deaths: 49 associated with cancer and 18 from intercurrent causes. None of the tested factors was significant on overall survival. In univariate analysis, the following three factors affected the specific survival: MATVFLAB (P=0.025), TLGFLAB (P=0.04) and TLGseuil (P=0.04). In multivariate analysis, only MATVFLAB had a significant impact on specific survival (P=0.049): MATVFLAB<18 cm(3): 31.2 months (95%CI: 21.7-not reached) and MATVFLAB>18 cm(3): 20 months (95%CI: 11.1-228.9). CONCLUSION: The metabolically active tumour volume measured with the automatic segmentation software FLAB on baseline PET-CT was a significant prognostic factor, which should be tested on a larger cohort.

Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs.

REASONS FOR PERFORMING STUDY: Ingestion of sycamore seeds (Acer pseudoplatanus) is the likely source of hypoglycin A in atypical myopathy (AM) but ingestion of seedlings in spring might also contribute to intoxication. OBJECTIVES: To test for hypoglycin A in seeds and seedlings collected on pastures where AM cases were reported and compare its concentration in serum of affected and healthy horses. STUDY DESIGN: Field investigation of clinical cases. METHODS: Whenever present, samaras (the winged nuts that each contain one seed) and/or seedlings were collected from pastures of 8 AM cases and 5 unaffected horses from different premises. Two AM cases were each co-grazing with an apparently healthy horse. Acylcarnitines and hypoglycin A were quantified in blood samples of all horses involved in the study. RESULTS: Hypoglycin A was detected in serum of AM (5.47 ± 1.60 µmol/l) but not in healthy controls pasturing where A. pseudoplatanus trees were not present. However, hypoglycin A was detected at high concentrations (7.98 µmol/l) in serum of a clinically healthy horse grazing a pasture with seedlings and samaras and also in the 2 healthy horses co-grazing with AM cases (0.43 ± 0.59 µmol/l). Hypoglycin A was detected in all samples of seeds and spring seedlings of A. pseudoplatanus. CONCLUSIONS: Atypical myopathy can be associated with the ingestion of sycamore samaras and also ingestion of seedlings. Hypoglycin A can be detected in the blood of horses with no detectable clinical signs at pasture in which there is A. pseudoplatanus. Determination of hypoglycin A concentration in blood is useful for screening for exposure in suspected cases of AM.

[Are extensive fields useful for radiotherapy of esophageal cancer?]. / Des marges extensives sont-elles nécessaires pour la radiothérapie du cancer de l'œsophage ?

PURPOSE: Study of the pattern of relapse for locally advanced oesophageal cancer and analysis of the local recurrences according to irradiated volume. PATIENTS AND METHODS: We performed a monocentric retrospective study of patients treated in the integrated centre of oncology (Angers, France). Two treatment strategies were used: concurrent chemoradiation alone or followed by surgery. Recurrences were classified as: locoregional, either isolated or associated with distant metastasis, and metastatic only. Locoregional relapses were subclassified as in-field, out-field, or mixed. RESULTS: Between March 2004 and October 2011, 168 patients were treated: 130 by chemoradiation, and 38 by chemoradiation followed by surgery. The median supero-inferior margins added to the gross tumour volume in order to create the planning tumour volume was 5cm (range: 0.5-21). Sixty-two percent of patients (n=104) relapsed: 82 locoregional relapses (49%), including 45 isolated relapses (27%) and 37 associated with distant metastasis relapses (22%), and 22 metastatic relapses (13%). From the 82 locoregional relapses, only four isolated relapses were exclusively out-field. CONCLUSION: With 5cm supero-inferior margins added to gross tumour volume, less than 3% of patients had an isolated out-field recurrence. However, half of the patients suffered in-field local recurrence and one third had metastases. These findings advocate for a limited prophylactic nodal irradiation. Trials are ongoing to assess dose escalation or surgery in order to increase local control.

[Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the upper urinary tract]. / Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation", "chemotherapy", and adjuvant.

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. / Sites de récidive après radiothérapie conformationnelle avec modulation d'intensité des carcinomes épidermoïdes des voies aérodigestives supérieures.

PURPOSE: The implementation of intensity-modulated radiotherapy (IMRT) in a centre requires regular critical review of medical practices and feedback to optimize the subsequent management of patients. PATIENTS AND METHODS: We reviewed and determined through a retrospective single-centre study recurrence sites of 167 consecutive patients treated for head and neck squamous cell carcinoma excluding skin or sinuses. Patients had mostly stage III or IV locally advanced cancer (n=123). RESULTS: Locoregional control rates at 1 and 2 years were respectively 87.9% (95% confidence interval [95%CI]: 81.6%-92.1%) and 77.6% (95%CI: 70.1%-83.5). Among 55 relapses, 20 patients (36.4%) had treatment failures. Patients treated with 70 Gy relapsed mainly in high risk volume (78%). Those treated with 66 Gy recurred regionally outside the irradiated volume (n=4) or in the irradiated high risk volume (n=3) or had isolated metastatic failure (n=3). Those irradiated with 50 Gy had regional relapse outside the irradiated volume (n=2) or isolated metastatic relapse (n=2). We noticed respectively 5.4%, 10.2% and 4.2% isolated metastatic, local, cervical lymph node relapse. CONCLUSION: Our results are consistent with data from the literature. Corrective actions were performed to enhance our practices.

Prevalence of naturally occurring cartilage defects in the ovine knee.

OBJECTIVE: To determine the prevalence, anatomical location and severity of cartilage defects in the stifle (knee) within a population of adult ewes (N = 65). MATERIALS AND METHODS: Articular cartilage (AC) of the distal femur, proximal tibia and patella was assessed using Osteoarthritis Research Society International (OARSI) recommendations for macroscopic and microscopic scoring of ovine cartilage. Synovial fluid analysis and histology of the synovial membrane were performed. All limbs were examined by computed tomography. RESULTS: Twenty-eight sheep (n = 28; 43%) presented at least one score 2 or score 3 lesion. Twenty-two (n = 22; 34%) sheep were macroscopically normal. Most frequent localizations of lesions were: axial aspect of the central third of the medial tibial condyle (32.7% of the lesions), middle third of the medial femoral condyle (29.4%), middle third of the articular surface of the patella (9.8%), and axial aspect of the central third of the lateral tibial condyle (9.8%). Grade of macroscopic lesions was significantly (H (3) = 29.31, P 0.000) affected by age. Macroscopic score correlated well with histological changes that can be found in osteoarthritis (OA) (r 0.83; P 0.000). Neither clinical signs of OA, nor cytological and histological signs of inflammation were identified, while imaging abnormalities were very rare. CONCLUSIONS: Our data seem to indicate that naturally occurring OA exists in ageing sheep, at least subclinically. It might be useful to take into account prevalent cartilage defects at baseline in studies using ovine models.

Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis.

BACKGROUND: Various treatments of osteoarthritis (OA) have been described, including use of nutraceuticals. OBJECTIVES: To review systematically the literature about the effects of nutraceuticals on clinical signs of pain or abnormal locomotion in horses, dogs, and cats, and to discuss methodological aspects of trials and systematic reviews. METHODS: A systematic search of controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs, and cats was performed, using Medline, CAB Abstracts, and Google Scholar. Scientific evidence was evaluated by means of criteria proposed by the Food and Drug Administration (FDA), and a scoring system adapted from both the CONsolidated Standards of Reporting Trials (CONSORT) statement and recommendations for assessing trials by the Center of Evidence Based Medicine of Oxford. RESULTS: Twenty-two papers were selected and reviewed, with 5 studies performed in horses, 16 in dogs, and 1 in cats. The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs. There were limited numbers of rigorous randomized controlled trials and of participants in clinical trials. CONCLUSIONS AND CLINICAL IMPORTANCE: The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs. Greater access to systematic reviews must be part of the objectives of the veterinary science in the future. Their reporting would be improved by internationally agreed-upon criteria for standards and guidelines.

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs.

The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 µg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (µg/mL) can be predicted taking into account the OTC concentrations in plasma (µg/mL), according to the following equation: OTC(nasal secretions) = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non-compartmental analysis. In plasma, the maximum concentration of drug (C(max) ), the time at which this maximum concentration of drug (T(max) ) was reached, the elimination half-life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 µg/mL, 4.0, 5.1 h and 150 µg·h/mL. In nasal secretions, C(max) , T(max) , t½ and AUC were, respectively, 6.29 µg/mL, 4.0, 6.6 h and 51.1 µg·h/mL.

Penetration of enrofloxacin into the nasal secretions and relationship between nasal secretions and plasma enrofloxacin concentrations after intramuscular administration in healthy pigs.

The pharmacokinetic behaviour of enrofloxacin (ENRO) in plasma and nasal secretions of healthy pigs was investigated, after a single-dose intramuscular administration of 2.5 mg/kg body weight of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. Concentrations of ENRO and its active metabolite ciprofloxacin (CIPRO) were determined in plasma and nasal secretions by high-performance liquid chromatography (HPLC). CIPRO was not detected probably because we investigated young weaned pigs. The data collected in 12 pigs for ENRO were subjected to noncompartmental analysis. In plasma, the maximum concentration of drug (C(max)), the time at which this maximum concentration of drug (T(max)) was reached, the elimination half-life (t(1/2)(beta)) and the area under the concentration vs. time curve (AUC) were, respectively, 694.7 ng/mL, 1.0 h, 9.3 h and 8903.2 ngxh/mL. In nasal secretions, C(max), T(max), t(1/2)(beta) and AUC were, respectively, 871.4 ng/mL, 2.0 h, 12.5 h and 11 198.5 ngxh/mL. In a second experiment conducted in 10 piglets, the relationship between concentrations of ENRO measured in the plasma and the nasal secretions has been determined following single-dose intramuscular administration of 2.5, 10 or 20 mg/kg body weight of the drug. It has been demonstrated that, among several variables, i.e., (1) the dose administered, (2) the time between intramuscular injection and blood sampling, (3) the age, (4) the sex, (5) the animal body weight and (6) the plasma concentration of the drug, only the latter influenced significantly the ENRO concentration in nasal secretions. Practically, using a generalized linear mixed model, ENRO concentrations in the nasal secretions (microg/mL) can be predicted taking into account the ENRO concentrations in plasma (microg/mL), according to the following equation:

Pre-study and in-study validation of an ultra-high pressure LC method coupled to tandem mass spectrometry for off-line determination of oxytetracycline in nasal secretions of healthy pigs.

In order to quantify oxytetracycline (OTC) in nasal secretions of healthy pigs after intramuscular injection of OTC at doses of 10, 20 and 40 mg/kg bodyweight, an original method based on ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was developed and fully validated. Sample preparation consisted in protein precipitation preceded by the addition of a releasing protein reagent. Metacycline (MTC) was used as internal standard. Separation was carried out at 65 degrees C in the gradient elution mode on a short analytical column filled with Acquity BEH C(18) stationary phase. The mobile phase consisted in a mixture of water and acetonitrile containing 1 mM of oxalic acid and 0.1% (v/v) of formic acid. The triple quadrupole mass spectrometer operated in the positive electrospray ionization mode; OTC and MTC were detected using multiple reaction monitoring. The pre-study and in-study validation of this bioanalytical method was performed by applying a novel strategy based on total measurement error and accuracy profiles. The maximum risk of observing future measurements falling outside the acceptance limits during routine as well as the measurements uncertainty were also estimated.

Characterisation of the acute and reversible airway inflammation induced by cadmium chloride inhalation in healthy dogs and evaluation of the effects of salbutamol and prednisolone.

The aims of this study were firstly to characterise a model of subclinical and reversible bronchial inflammation induced by cadmium chloride inhalation in healthy dogs and then to examine the effect of prednisolone or salbutamol treatment on the resulting bronchitis. The model characterisation and the effects of treatment were studied using clinical symptoms, haematology, thoracic radiography, bronchoscopy and bronchoalveolar lavage, barometric whole-body plethysmography and histamine broncho-provocation tests. In addition, the activity of matrix metalloproteinases (MMP)-2 and -9 were determined in serum and bronchoalveolar lavage fluid (BALF). Cadmium inhalation induced: (1) a transient bronchial inflammation, dominated by neutrophils; (2) a neutrophilia of the blood that persisted for up to 4 weeks; (3) a transient increased bronchial reactivity, and (4) a significant increase in MMP-9 activity in the BALF. Prednisolone treatment reduced the influx of inflammatory cells into the BALF, but not significantly, had no effect on pulmonary function, and did not reduce of airway hypersensitivity. Salbutamol had almost no effect on any of the parameters investigated.

Liquid chromatographic determination of enrofloxacin in nasal secretions and plasma of healthy pigs using restricted access material for on-line sample clean-up.

A new fully automated method was developed for the quantitative analysis of an antibacterial drug, enrofloxacin (ENRO), in both nasal secretions and plasma samples of healthy pigs. The method is based on the use of a pre-column packed with restricted access material (RAM), namely RP-18 ADS (alkyl diol silica), for on-line sample clean-up coupled to a liquid chromatographic (LC) column containing octadecyl silica. The only off-line sample preparation was the 50-fold dilution of nasal secretions and plasma samples in the washing liquid composed of 25 mM phosphate buffer of pH 7.4. A 10 microl diluted sample volume was injected directly onto the pre-column and washed for 7 min. By rotation of a switching valve, the analyte of interest was eluted in the back-flush mode with the LC mobile phase which consisted in a mixture of 25 mM phosphate buffer of pH 3.0 and acetonitrile according to a segmented gradient elution. By a new rotation of the switching valve, the pre-column and the analytical column were equilibrated for 3 min with the initial mobile phases. The flow-rate was 0.8 ml min(-1) for the washing liquid and 1.5 ml min(-1) for the LC mobile phase. ENRO was detected by fluorescence at excitation and emission wavelengths of 278 and 445 nm, respectively. Finally, the developed method was validated using an original strategy based on total measurement error and accuracy profiles as a decision tool. The limits of quantitation of ENRO in plasma and in nasal secretions were 30.5 and 91.6 ng/ml, respectively. The validated method was then applied successfully to the determination of ENRO in healthy pigs treated by intramuscular injection at different doses (2.5, 10 and 30 mg/kg bodyweight) for a pilot study. This method could be also used for the simultaneous analysis of ENRO and its main metabolite, ciprofloxacin (CIPRO).

The effect of colic on oxygen extraction in horses.

Blood oxygen transport and oxygen extraction were assessed in horses with colic. A gravity score (GS) ranging from 1 to 3 was attributed to each colic case with healthy horses used as controls. Jugular venous and carotid arterial blood samples were collected and concentrations of 2,3-diphosphoglycerate, adenosine triphosphate, inorganic phosphate and chloride were determined. pH and partial pressures of carbon dioxide (PCO(2)), and oxygen (PO(2)) were also measured. Oxygen equilibrium curves (OEC) were constructed under standard conditions and oxygen extraction ratios calculated. Haemoglobin oxygen affinity measured under standard conditions (P50(std)) was unchanged in colic horses compared with healthy controls. Horses with the highest GS, i.e. 3 had lower blood pH values than healthy animals. Arterial and venous partial pressures of oxygen at 50% haemoglobin saturation (P50(a) and P50(v)) were significantly higher in horses suffering from colic (GS=3) than in healthy horses. The oxygen extraction ratio was also significantly increased in colic horses with a GS of 3. A rise in the oxygen extraction ratio detected in the most severely affected animals seemed to reflect the compensatory properties of the oxygen transport system where extraction of oxygen from the blood increases when systemic oxygen delivery decreases, as might be anticipated in horses with colic.

Efficacy of ceftiofur and flunixin in the early treatment of bronchopneumonia in weaners.

Three groups of five pigs were inoculated intratracheally with Escherichia coli lipopolysaccharides, and 24 hours later with 10 x 10(9) colony-forming units of a non-toxigenic strain of Pasteurella multocida type A; a fourth group was left uninoculated as controls. The three inoculated groups received either no treatment (positive controls), or were treated with 3 mg/kg ceftiofur intramuscularly once a day for five consecutive days, either alone or combined with 2 mg/kg flunixin intramuscularly once a day for three consecutive days. The sustained coughing and hyperthermia recorded in the positive controls disappeared after two days and three days of treatments, respectively, in the treated animals, and the reductions in daily weight gain and changes in breathing pattern observed in the controls were not observed in the treated animals. There were no significant differences between the pigs treated with ceftiofur alone or ceftiofur combined with flunixin. In the positive controls, the number of inflammatory cells in samples of bronchoalveolar lavage fluid continued to increase up to 15 days after inoculation, whereas in the treated animals there were similar increases at six days but the numbers had decreased to baseline levels after 15 days. Similarly, in the treated animals the volume of the lung lesions was significantly less than in the control animals, but the inclusion of flunixin in the treatment regimen had no significant additional effect.

[Development of a model of asthma in the cat: veterinary and medical concerns]. / Développement d'un modèle d'asthme chez le chat: intérêt vétérinaire et biomédical.

Feline asthma is a respiratory disorder, which is poorly studied in veterinary medicine and whose therapeutical approach is not based on pre-clinical or clinical studies. Besides the need to establish therapeutical strategies using bronchodilators and anti-inflammatory drugs, the asthmatic cat presents some interest as animal model of human asthma. Given the body size of a cat and the similarities of pathophysiology between feline and human asthma, simultaneous and repeated investigations of lung function, airway inflammation and airway remodelling in response to an allergic stimulus might be performed in felines. The experimental model of feline asthma developed by our laboratory allows, by respecting animal well-being, (1) the non invasive investigation of lung function and airway responsiveness using barometric whole body plethysmography, (2) the investigation of lower airway inflammation by determining hydrogen peroxide in exhaled breath condensate and by analysing bronchoalveolar lavage fluid, (3) the assessment of morphological changes based on thoracic radiography, bronchoscopic scoring and bronchial biopsies. This experimental model allows, on one hand, to elaborate therapeutical approaches for spontaneously asthmatic cats and, on the other hand, the testing of innovative treatments against asthma.

Effects of intravenous infusions of sodium bicarbonate on blood oxygen binding in calves with diarrhoea.

Twelve diarrhoeic calves were treated intravenously with an isotonic solution containing sodium bicarbonate, and their oxygen equilibrium curves (OECS) were calculated under standard conditions and compared with those of a group of healthy calves. The relationships between the OECS for arterial and venous blood and the oxygen extraction ratio were investigated. In the diarrhoeic calves, the affinity of haemoglobin for oxygen, measured under standard conditions, was increased compared with the healthy animals. During the infusion, the standard partial oxygen pressure at 50 per cent saturation of haemoglobin (P50) values stayed below the values recorded in the healthy animals. At the end of the infusion the mean standard P50 of the diarrhoeic calves was lower than before the infusion. The combined effects of all the regulating factors on blood oxygen binding resulted in the OECS of the arterial and jugular venous blood of the diarrhoeic calves remaining unchanged compared with the healthy calves. However, the administration of the infusion decreased the P50 of both the arterial and venous blood to below the value recorded in the healthy calves. Oxygen extraction by the tissues was impaired in the diarrhoeic calves throughout the infusion, and they remained dehydrated and depressed until 120 minutes after the infusion began.

Blood-oxygen binding in healthy Standardbred horses.

The purpose of this study was to determine the effect of regulating factors on the oxygen equilibrium curve (OEC) under standard conditions and then to calculate the oxygen extraction between arterial and jugular venous blood in healthy Standardbred horses. The results were compared to those previously obtained in humans and cattle, using the same experimental method. The partial oxygen pressure at 50% saturation of haemoglobin, measured under standard conditions (standard P50), was 24.8+/-2.0 (SD of mean) mmHg. This value was similar to the cattle standard P50 (25.0+/-1.4 mmHg, SD of mean) but lower than the human standard P50 (26.6+/-1.2 mmHg, SD of mean) previously reported using the same experimental method. The effects of regulating factors on the standard OEC were also determined, and a major effect of pH and temperature was noted. In contrast, partial carbon dioxide pressure played only a minor role in horses, compared to cattle and humans. No significant correlation was found between phosphate and chloride concentrations and standard P50.

Haemoglobin oxygen affinity and regulating factors of the blood oxygen transport in canine and feline blood.

Complete dynamic oxygen equilibrium curves (OEC) on dogs and cats whole blood were measured at 33, 37 and 41 degrees C. OEC were also run at three partial carbon dioxide pressures (20, 40 and 80 mmHg) as well as at five pH levels (7.2, 7.3, 7.4, 7.5 and 7.6). 2,3- diphosphoglycerate (DPG) concentrations were determined. Results were compared to those previously published in humans, using the same experimental method [Comp. Biochem. Physiol. 106 (1993) 687]. In standard conditions (pH 7.4, pCO2 40 mmHg and temperature 37 degrees C), the partial oxygen pressure at half-saturation of haemoglobin (p50) was 30.0+/-1.3 mmHg for dogs and 34.1+/-1.8 mmHg for cats. Cat's OEC was thus rightshifted compared to dog's OEC, itself rightshifted compared to human OEC. 2,3-DPG concentrations were higher in dogs than in men until they were very low in cats. Contrary to that observed in human medicine, no significant correlation was identified between standard p50 and canine 2,3-DPG values. Influence of pH, pCO2 and temperature on the OEC was saturation dependent. In dogs, Delta log p50/Delta pH was equal to -0.370, Delta log p50/Delta log pCO2 was 0.093 and Delta log p50/Delta T was 0.020. In cats, Delta log p50/Delta pH was equal to -0.405, Delta log p50/Delta log pCO2 was 0.080 and Delta log p50/Delta T was 0.016. Practically, temperature and pH variations exert a lesser influence in domestic carnivores than in humans, effect of pCO2 being similar in both.